(1) Field of the Invention
This invention relates generally to the field of plastic and reconstructive surgery and, more particularly, to methods for soft tissue augmentation using growth factors.
(2) Description of the Related Art
Many procedures in plastic and reconstructive surgery involve the correction of soft tissue contour defects. Patients with conditions like hemifacial microsomia, Romberg's disease, traumatic injuries, cancer resection surgeries, and depressed scars as seen following severe acne, chicken pox or smallpox all suffer from substantial soft tissue contour defects. In addition, the desire to enlarge a soft tissue site might produce a need for augmentation such as breast or penile augmentation. Such conditions requiring contour correction or enlargement are usually reconstructed with flaps of autogenous tissue, with alloplastic implants or with prosthetic implants. Flap reconstruction often involves extensive surgical procedures that can lead to significant donor site morbidity and scarring. Furthermore, implants have the disadvantage that they can migrate, extrude, become infected, or cause painful and deforming capsular contractures.
Tissue augmentation with injections of autologous fat is an approach that avoids prosthetic implants or a surgical procedure. Nevertheless, because the injected fat is avascular, it resorbs over time. It would, therefore, be desirable to have a method for augmenting soft tissues to generate stable, localized deposits of vascularized adipose tissues and it would further be desirable if the method were nonsurgical.
Previous studies have demonstrated that substances such as dexamethasone can be administered systemically to influence the growth of regional fat deposits. Chronic, systemic administration of dexamethasone resulted in an increase in fat deposits in certain regions and this increase was due to both an increase in cell size, i.e. hypertrophy, and an increase in cell number, i.e. hyperplasia (Angel et al. 134-140, 1982). In man, systemic administration of adrenal corticosteroids are known to produce characteristic and undesirable changes in fat distribution. These changes are considered a detrimental side effect and typically include deformities referred to as "moon facies" and "buffalo humps". Paradoxically, local subcutaneous administration of steroids is known to cause fat atrophy. Thus, steroids have not been shown to produce a localized increase in fat growth when administered at a particular target site.
One group of substances known to be growth factors are the insulin-like growth factor family of peptides which include insulin, Insulin-Like Growth Factor-I (IGF-I) and Insulin-Like Growth Factor-II (IGF-II). (Froesch et al., Ann Rev Physiol 47:443-67, 1985 which is incorporated by reference). Insulin is known to be a lipogenic growth factor. Because of this property, the use of insulin could provide a possible approach for stable soft tissue augmentation, however, insulin is also capable of producing a potent hypoglycemic effect. On the other hand, IGF-I, is another member of the insulin-like growth factor family of peptides, similar to insulin in structure and function. IGF-I produces lipogenesis in epididymal fat pads and hypoglycemia in rats and inhibition of lipolysis in human fat cells apparently mediated through insulin receptors although IGF-I was less potent than insulin in these actions (Schmitz et al. Diabetologia 34:144-149, 1991; Bolinder et al., J Clin Endrocrinol Metabol 65:732-737 which are incorporated by reference). In contrast to these actions mediated through the insulin receptor, IGF-I can also act to stimulate growth and development through specific high-affinity type I IGF receptors that are distinct from insulin receptors mediating lipogenesis. (Adamo et al., BioFactors 3:151-157, 1992; Frosch et al., 1985 which are incorporated by reference). An action of IGF-I at these receptors might be expected to produce a stimulation of growth without eliciting a hypoglycemic effect. IGF-II and Insulin, at high concentrations, are also known to bind to IGF-I receptors. Furthermore, IGF-II can also stimulate growth although this substance is about one-third as potent as IGF-I in stimulating DNA synthesis in human fibroblasts. (Id.). Nevertheless, none of the peptides from the insulin-like growth factor family of peptides have been utilized heretofore for promoting localized growth of soft tissues in an individual.